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Journal of Neuroscience, Vol 16, 2172-2178, Copyright © 1996 by Society for Neuroscience

ARTICLE

NMDA receptor upregulation: molecular studies in cultured mouse cortical neurons after chronic antagonist exposure

P Follesa and MK Ticku
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764, USA.

We examined the possibility of changes in gene expression of the NMDA receptor subunits after chronic antagonist treatment. Exposure of neurons to the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP-5) produced an increase in the levels of the R2B mRNA subunit. Concomitant exposure of neurons to AP-5 and NMDA reversed the upregulation. Chronic AP-5 treatment increased the R1 polypeptide, whereas no change was observed in the levels of mRNA encoding the R1 subunit. A more pronounced increase was observed in the R2A/B polypeptides. These data demonstrate that chronic treatment with NMDA antagonists selectively upregulates the NMDA receptor mRNAs and polypeptides. Furthermore, antagonist treatment produced a differential regulation of the R1, R2A, and R2B subunits in cortical neurons.

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